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Testosterone Replacement for Menopausal Women

Am Fam Physician. 2001 Mar 15;63(6):1199-1203.

Before menopause, the average woman produces 300 μg (1,040 nmol) of testosterone daily. Nearly equal amounts of the hormone are derived from the adrenal glands and the ovaries. Women who undergo bilateral oophorectomy before natural menopause sustain about a 50 percent decrease in serum testosterone levels and an 80 percent decline in estradiol concentrations. Estrogen replacement therapy is a common treatment for these women. Studies have shown that women who undergo surgical menopause have a decrease in sexual drive, activity and pleasure, and a decreased sense of well-being. Shifren and colleagues performed a study to determine if physiologic doses of testosterone therapy were safe and beneficial in women with surgically induced menopause.

The study enrolled women between 31 and 56 years of age who had undergone hysterectomy and bilateral oophorectomy before natural menopause. The surgery had to have been performed at least one year, but not more than 10 years, before enrollment. Additional entry criteria included a serum testosterone level of less than 30 ng per dL (1.0 nmol per L), daily oral estrogen and a stable, monogamous, heterosexual relationship of at least one year. Potentially eligible women completed a Brief Index of Sexual Functioning for Women questionnaire that addressed 22 items pertaining to aspects of female sexuality. The scoring for the survey ranged from −16 (poor functioning) to +75 (maximal functioning). Women who participated in the study had to have a score less than 33.6, the mean for normal women.

Following initial screening, the women were randomized to receive two transdermal patches for twice weekly application. The patches consisted of two placebos, one placebo and one 150-μg per day patch or two 300-μg per day patches. Each woman underwent three 12-week courses of therapy. Serum testosterone levels were measured at weeks 4, 8 and 12 of each cycle. In addition, serum lipids, glucose and liver function were monitored regularly. Finally, the index of sexual functioning questionnaire was administered at the end of each 12-week period, and mood was assessed by the Psychological General Well-Being Index. The latter instrument scores mental health issues.

Seventy-five women with a mean age of 47 years were enrolled in the study. Sixty-five women completed enough of the study to provide data that were included in the intent-to-treat analyses. Women who used the 300-μg patches had serum testosterone levels that reached high-normal levels, and those who used the 150-μg patches had mid-normal levels. The levels of the placebo group remained at low or low-normal.

The mean composite scores on the sexual functioning index increased from a mean of 52 at baseline to 72 in the placebo group, to 74 in the 150-μg group, and to 81 in the women who received the 300-μg per day dose of testosterone. The percentage of women who had sexual intercourse at least weekly increased from 23 percent at baseline to 35 percent in the placebo group and the 150-μg group, and up to 41 percent in the 300-μg group. The mean total scores on the psychologic well-being index were 78 at baseline and increased with both doses of testosterone, although the change in scores was only significant in the women taking 300 μg per day. Finally, no significant changes were found in the degree of acne, hirsutism, total cholesterol levels, fasting glucose levels or liver function results.

The authors conclude that testosterone replacement in women who undergo surgically induced menopause produces significant increases in sexual functioning and psychologic well-being. The benefits are more pronounced with higher doses of testosterone.

editor's note: This study adds further evidence to what has been shown in other studies—that testosterone has a positive effect on libido in menopausal women. One of the interesting, but perhaps not surprising, aspects of this study was the high response rate to the placebo patches. In an accompanying editorial, Guzick and Hoeger note that the relationship of androgens to mood and sexual functioning in women is still controversial. They also cite concerns about the adverse effects of longer courses of testosterone therapy than were used in this study. Nonetheless, they do agree that this study showed a definite benefit with a 300-μg dose of testosterone, and other data have shown a possible benefit of androgens on bone mineral density. For now, physicians may want to consider short courses of androgens in select female patients.—j.t.k.